Mechanisms of haemopoietic stem cell mobilisation: Role of the cross-talk between bone marrow and bone.

Funding Activity

Website
http://purl.org/au-research/grants/nhmrc/434515

Funding Status
Closed

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Funded Activity Summary

Blood or Haematopoietic stem cells (HSCs) are found in the bone marrow and make all the blood cells we require life-long. This process must be carefully regulated. The production of too many blood cells leads to leukaemia while too little means anaemia. However we still have much to learn on how this regulation occurs. Scientists have recently found that osteoblasts (the cells that normally form bone) are responsible for some of this regulation. In fact osteoblasts create a type of 'home' for HSCs. Our laboratory has recently found that this relationship also works the other way around. That is bone marrow cells themselves regulate osteoblast numbers and thus bone formation. To show this, we used a therapy that forces haematopoietic stem cells to leave the bone marrow and migrate into the blood (a process called mobilisation). Mobilisation is used clinically to harvest large numbers of HSCs for transplantation into cancer patients to prevent bone marrow failure following chemotherapy. To our surprise, we found that when we mobilise HSCs, the rate of bone formation dropped. As osteoblasts (the bone forming cells) are also involved in creating the HSC 'home', we aim to test whether treatments which increase bone formation boost the number of HSCs that are available to be mobilised and collected for transplantation. Thus, by manipulating bone formation we may ultimately be able to improve the long-term survival rates of cancer patients that require high dose chemotherapy and subsequent transplantation. This proposal also aims to better understand (i) how blood-forming cells control bone formation, and reciprocally (ii) how bone-forming cells regulate haematopoietic stem cells in the bone marrow.

Funded Activity Details

Start Date: 01-01-2007

End Date: 01-01-2009

Funding Scheme: NHMRC Project Grants

Funding Amount: $461,196.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Cellular Interactions (incl. Adhesion, Matrix, Cell Wall)

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

Bone | Bone formation | Bone marrow | Haematological disorders | Haematopoiesis | Haematopoietic stem cell mobilisation | Haematopoietic stem cell transplantation | Microenvironment | Osteoblast | Osteoporosis

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